Nasopharyngeal carcinoma (NPC) occurs much more commonly in southern China and Taiwan than in other parts of the world. Epstein-Barr virus is suspected to play a role in disease etiology, but supporting data are quite limited. The disease exhibits clear familial aggregation, and our previously reported segregation analyses suggest that a recessively transmitted major gene may be involved. Our current studies are aimed at determining the basic causes of this disease using molecular epidemiological approaches. We have obtained questionnaire data regarding the family history of this disease and correlation with risk factors from a large number of subjects. We have identified and recruited over 150 families suitable for sampling for gene mapping studies based on linkage and/or linkage disequilibrium approaches and have obtained samples of blood, oral rinses, and tumor tissues as well as extensive risk factor questionnaire data. Our laboratory has analyzed highly polymorphic DNA markers in several regions of the genome suspected to be involved in this form of cancer, including the HLA region on chromosome 6. These data are being scored using our semi-automated analysis software in preparation for statistical analyses to search for major genes involved with disease susceptibility. We have also initiated contacts on Mainland China and traveled there to assess the feasibility of establishing new sites for collection of additional families there in the future. Statistical analyses will be performed for the genetic markers already characterized in a small, preliminary sample of NPC families. Molecular analyses of p53, EBV and other appropriate markers such as those in regions known to be associated with Loss of Heterozygosity (LOH) will also be conducted on available tumor tissues. Major efforts are continuing in family recruitment in China and a genome scan of the existing collection of 800 study subjects began in our laboratory in 1998.